This project will take advantage of the unique opportunity presented by the Vietnam Era Twin (VET) Registry to evaluate potential biologic markers for familial vulnerability to the development of PTSD. Subjects will include twins discordant for combat exposure. Several know biologic PTSD markers will be evaluated by comparing their presence in the (high-risk) unexposed monozygotic (Mz) co-twins of exposed twins with combat-related PTSd versus the (low-risk) unexposed Mz co- twins of exposed twins without combat-related PTSD. A limited sample of (medium-high-risk) unexposed dizygotic (Dz) co-twins of exposed twins with combat-related PTSD will be recruited in order to test whether any identified familial biologic vulnerability factor for PTSD represents the produce of heredity. An additional aim is to examine susceptibility to mental disorder as a familial, possibly inherited, vulnerability factor for PTSD by performing comprehensive psychodiagnostic interviews on subjects in an design parallel to that employed for the PTSD biologic markers. Another aim is to evaluate potential acquired biologic PTSD signs by comparing exposed PTSD twins versus their unexposed Mz co-twins. Dependent variables will include (a) autonomic and muscular startle responses and their habituation; (b) amplitude of the P3 event-related potential (ERP) component in a target discrimination task; (c) slope of the P2 ERP component as a function f tone intensity in a stimulus intensity modulation experiment; and (d) suppression of salivary cortisol following low-dose oral dexamethasone. Each marker to be studied is non-invasive; can be measured on an ambulatory basis; has been shown in previous, published, peer-reviewed research to significantly differentiate PTSD and non-PTSD subject groups; and is capable of being informed by the data to be obtained in the proposed project. Subjects will be diagnosed by a field psychologist using the Clinician- Administered PTSD Scale, Structured Clinical Interview for DSM-IV, and other instruments. Dependent variables will be measured at a traveling field psychophysiology laboratory set up at a VA Medical Center or Vet Center near the subject's home. Statistical significance will be tested by means of univariate and multivariate analyses of variance and covariance and independent t-tests performed on key groups, and selected subgroups. Results are expected to advance our understanding of the constitutional versus acquired nature of biologic abnormalities in PTSD and the pathogenesis of this disorder. Results will also have implications for the prophylactic screening of persons at high risk for the development of PTSD upon exposure to military combat or other severe stressors.